73 Disorders of Growth
Statural growth is an integral part of childhood development and normally occurs in a predictable pattern. Families often seek medical attention when a child does not seem to grow adequately, and the pediatrician’s primary responsibility is to differentiate between normal variants of growth and abnormal patterns (i.e., between a healthy petite child and a child with an underlying systemic illness or other growth problem). Because early detection is important for diagnosing any underlying illness and intervening to maximize potential adult height, interval growth should be accurately assessed and plotted on a growth chart at each health maintenance visit. When judging a child’s growth, it is useful to determine the sex-adjusted midparental height (genetic target height) by adding together the heights of the biological parents and adding 5 inches (13 cm) for a boy or subtracting 5 inches (13 cm) for a girl and then dividing by 2. This height, plus or minus approximately 4 inches, represents an estimate of the child’s genetic height potential. Any deviations from normal growth patterns or the child’s genetic height potential should be evaluated; the more the child’s growth deviates from the usual pattern, the greater the chances of an underlying abnormality.
Etiology and Pathogenesis
Normal Growth Patterns
Normal growth follows a predictable pattern. This pattern is depicted in widely used growth charts, which comprise sequential percentile curves showing the distribution of selected body measurements (usually length or height, weight, and weight for height or body mass index [BMI]) in children of a country. Growth is fastest during the fetal period; fetal size primarily relates to maternal health and nutrition. During infancy, the child’s genetic factors come into play. Growth gradually slows, with average increase in length of 25 cm over the first year of life and 10 cm over the second year. In this period, infants often cross length percentiles (channelize) to a percentile more in line with their genetic potential. After the second birthday, growth proceeds at a slow, relatively constant velocity of 4 to 6 cm/y, and shifting percentile channels is abnormal. Childhood growth is slowest just before the onset of puberty and then accelerates during adolescence, resulting in the pubertal “growth spurt” (average growth velocity of 10 cm/y). At the end of puberty, growth ceases as the epiphyses (growth plates) fuse.
Longitudinal Growth and Mediating Factors
Longitudinal growth occurs via chondrocyte proliferation and subsequent endochondral ossification in the growth plates of long bones (and vertebrae). The growth plate is a cartilaginous zone located between the metaphysis and epiphysis (secondary ossification zone at the end of the bone). Growth is a complex process regulated by multiple factors, including nutrition, hormones, and growth factors that act either locally within the growth plate or systemically.
Growth hormone (GH) is the most important growth-regulating hormone; its pulsatile secretion from the anterior pituitary somatotrophs is regulated by two hypothalamic peptide hormones, GH-releasing hormone (GHRH) and somatostatin, which, respectively, stimulate and inhibit its release (Figure 73-1). Circulating GH is bound to GH-binding protein (GHBP), which corresponds to the extracellular domain of the GH receptor. Many, although not all, of GH’s actions are mediated through insulin-like growth factor (IGF)-I (i.e., somatomedin-C). Serum IGF-I is produced principally in the liver in response to GH and circulates in the bloodstream bound to IGF-binding proteins (especially IGFBP-3) that control its bioavailability. IGF-I acts at target tissues by binding cell-surface IGF receptors and triggering multiple downstream effects that include cellular hypertrophy and proliferation. IGF-I and free fatty acids also inhibit GH secretion at the level of the pituitary and hypothalamus.
Other systemic hormones that affect growth include insulin (the principal growth-promoting hormone in utero), androgens and estrogens (which induce the pubertal growth spurt and, in the case of estrogens, epiphyseal fusion), thyroid hormone (which has a permissive effect on GH secretion and exerts direct action at the growth plates), and glucocorticoids (which inhibit growth both centrally and at the growth plate).
Abnormal Growth
Abnormalities in growth can be caused by systemic illness, psychosocial deprivation, malnutrition, or abnormalities in the secretion or action of any of the aforementioned hormones and growth factors. Growth failure is defined as height velocity that is less than expected for a child’s age, sex, and pubertal stage or as the crossing downward of two or more major height percentiles (beyond 2 years of age). Growth failure always merits an evaluation. Normal height is a continuum; short stature is conventionally defined as a height that is below the child’s genetic potential (as determined by parental heights) or more than 2 standard deviations (SDs) below the mean for age and sex. Thus, approximately 2.5% of a population will be classified as short, including some healthy children. Because the average adult height differs considerably among different ethnic groups, the actual height that corresponds to short stature differs from population to population.
Clinical Presentation
The causes of short stature can be divided into three general categories: chronic disease (including undernutrition), familial short stature (FSS), and constitutional delay of growth and puberty (CDGP) (Figure 73-2). Endocrine diseases are rare causes of short stature and are distinguished from other causes of short stature by linear growth failure that is more significant than weight loss. In developed countries, most short children have FSS, constitutional growth delay, or both. Short stature and constitutional growth delay are diagnoses of exclusion. The following is a focused review of the clinical presentations of selected normal variants and causes of short stature; see Box 73-1 for a comprehensive list of growth disorders.
Figure 73-2 Growth curves and disorders of growth. Illustrative growth patterns are shown, as well as multiple factors that may impact a child’s growth. Many cases can be multifactorial.
Box 73-1 Differential Diagnosis of Short Stature
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